N-substituted carbamic acid esters



Patented Aug. 29, 195

PATENT? ornce N-'SUBSTITUTED,CAEBBAMIG ACID I l-SEEKS Karl H. Weber and Lowell. B.aleliilggrze,- Washington, C., assignors, by inesne -ass'ignme itsgto Lowell-B: Kilgoreand HelenFordKilgorefbdth of Washington, D. C.

No i Applica ion lunezzl 1945i Serial No. 6111,0115

where. B islselected' from'the group consisting of 'hxdmcarhon haloge m, his dival n glhylene and n is a smallwvhole number; and R" is selected from the group consisting of hydrocarbon, :heterocyclic and radicals of the type R! O '1X- wherein 'Xis; divalent alkylene and B4 is a hydrocarbon group. Ah'further'object o'f this invention is the' p rovision of a process for the preparation of these *N'-(e-ethecrifled-acetyl) oarbamic acid esters. .Still a further object of .this invention'is the, preparation of new chemijeals suitable 'for combating insects; 0 ther objects and advantages will appearhereinafter;

These ObJ ECtS are "accomplished-by the, followin g invention wherein N- (-a-etherifled acet-yl) ,carbamio acid esters are pregared'byreacting 'the acyl' halide ofan a-etherified acetic acid: with anester of carbamie acidas follows;

R ()A) n-OC1I2G,O C1FHH2NQOQRZ .BL-andR. may he the sameor difierent'organic ..ramcaIs,w

The esters of oarbamio acid which are used'as starting materials may be made by any one of several known methods, for example, by "heating urea withthe appropriate.aleoh'ohwxganio Syntained by heating together. acarbamic acid; ester ,andfl he acyl halide ojlall -etherified. acetic. acid over. varyin periods of. time depend n l th ireaoiivitiesof the. i dividual-co mponen s of the .neaoti'onnnux uree whene neeeessary a suita inert diluentlsuch as benzene or. toluene may h Similarly (01.260H7zh);

32-. used. To facilitate the removal of HCl suitable organic bases such as pyridine and the like may beaddedtorthereactionmixture.

"The more ezletailed practiee ofthe invention is illustrated by the following" examples -whieh, however, do not limit the scope of theinvention many may.

' EXAMPLE L Preparatiorm or bu'tyl :ZW-fsebutomyethomydcetfll oarbwmata H ramsoifthionymhloride and.132 grarn;s of 5-butoxyethoxyacetib acid dissolved H1500 cc; of benzene were refluxed together for; hours. Thenexcess thionyl'chloride was distilled difwi-th 199 cc.,ojf benzene. fiflgrar'nsof bu-tyl carbamate were added and the reaction mixture wastefiuxed for 2d hours. It was then washed successively with water; sodium "bicarbonate solution and again water. Distillation of the reaetion mixture under reduced pressure yielded-35 grams P of-e hut-x1; ,N-fiebutonxethoma etn. e arhamate wihieluboiledeatfi ABE 41mm Exemmnm .o'f o-buiowuethgl: e-ilzu oxyemosquacetlvjl carbamat'e wlaxe almtime. of: .tetbwhydnojmfwyk Iii-13:-windmillfi ethowyoeetylicmnbomote ;9..l. lemme or fi buliogiye,irethoxyethoxyacetio aeiii and 52.3 grams of thi'onyl chloride dissolved in '75, on 'fjbenzene were refluxed together for itlwolhonr.s. llxgess'thionyl chloride was removed distilling, fl 25 cc. I ofbenzen-e; 6 grams of tetrahydrofurfuryl carbamate were added and the solution was refluxed for 33 hours. The resulting reaction mixture was washed successively with water, sodium bicarbonate solution and again ExAMPLEe Preparation of fl-benzowyethyl' N-fJ-ethoacyethoxyacetyl carbamate grams of p-ethoxyethoxyacetic acid and" 4 grams of thionyl chloride dissolved in '75 cc. of benzene were refluxed for two hours. Excess thionyl chloride was'removed by distilling off 25 cc. of benxene. 6.7 grams of e-benzoxyethyl carbamate dissolved in 25 cc. of benzene were added and the reaction mixture was refluxed for 28 hours.

bonate solution and again water. under reduced pressurep yielded 4 grams of ,B-benzoxyethyl N-fi ethoxyethoxyacetyl carbamate 'which boiled at PTO-175 C./l mm.

Other members of the newseries of N-e-etheri- .fied-acety1' carbamic acid esters which we have prepared by the methods set out in'the aforedescribed examples are:

Butyl N-2,3,4,6-tetrachlorophenoxymethoxyacetyl carbamate Butyl N-fi-ethoxyethoxyacetyl carbamate Dodecyl N-B-ethoxyethoxyacetyl carbamate 'Isoamyl N-B-butoxyethoxyacetyl carbamate p-Phenoxyethyl N-fi-butoxyethoxyacetyl carbamate Phenethyl N-p-butoxyethoxyacetyl carbamate Cyclohexyl N-p-butoxyethoxyacetyl carbamate p-Ethoxyethyl N-B-phenoxyethoxyacetyl carbamate Ethyl N-B-benzoxyethoxyacetyl carbamate Propyl N-p-butoxy-p-ethoxyethoxyacetyl carbamate.

The new N- (a-etherified-acetyl) carbamic acid esters as a class possess valuable insect combating properties. When applied in the form of a lotion, spray, cream or salve, they effectively repel such dangerous and annoying pests as flies and mosquitoes.

The table demonstrates the effectiveness of representative members of this new series of organic compounds against the common house fly, Musca domestica. The test procedure used was the sandwich bait"- method substantially as described in Soap, June 1939, page 103 if. A coating of molasses was applied to one side of a strip of blotting paper and dried to a hard, glossy surface. It was covered with a strip of thin, porous tissue which had previously been immersed in a 5 per cent solution in alcohol of the compound to be tested and then dried-until the alcohol had evaporated. The concentration of the test solutions was reduced to 5 percent because the repellency of certain members of the series was so prolonged that the flies were in danger of dying before completion of the test. For comparison purposes one strip was treated only with solvent.

The strips prepared in this fashion were mounted on a board and introduced into a large cage containing more than 2000 hungry houseflies. By

'making readings at intervals, the duration of repellency, namely, the time which elapsed before the flies began to feed on the molasses through the treated tissue covers was observed.

TABLE.N (a ETHERIFIED ACETYL) CABBAMIC ACID ESTERS. REPELLENCY TO HOUSEFLIES IN 5 PERCENT CONCENTRATION Bait still untouched at end of this period. Test terminated to feed flies.

The resulting reaction mixture was" 1 washed successively with water, sodium bicar- Distillation f EXAMPLE 5 a. Butyl N-fi-butoxyethoxyacetyl carbamate, when applied to the forearm of an individual which was exposed to a cage full of hungry Ae'des aegyptz' mosquitoes, repelled the insects for anaverage of 182 minutes. ,7

b. Isoamyl N-fi-butoxyethoxy acetyl carbamate, when applied to the forearm of an individual which was exposed to a cage full of hungry Ae'des aegyptz' mosquitoes, repelled the insects for an average of 1 hour.

0. Propyl N-fl-butoxy-fi-ethoxyethoxyacetyl carbamate, when applied to the forearm of an in dividual which was exposed to a cage full 'of hungry A'des aegyptz' mosquitoes, repelled the insects for an average of .minutes.

These new N-(a-etherified-acetyl) carbamic acid esters may be employed by direct topical application or they may be incorporated into liquid or solid carriers. They'are especially useful as the active ingredients of insect-repellent lotions, creams, ointments and the like. They may be dis.- solved in liquid diluents such as alcohol, aqueous alcohol, ispropanol, dimethyl phthalate and hydrocarbon oils such as kerosene or emulsified in water, if necessary with the aid of a suitable dispersing agent. If desired they maybe admixed with finely divided carriers such as diatomaceous earth, talc, pyrophyllite, bentonite, etc.

Furthermore the new compounds of our invention may be combined with insecticidal materials such as pyrethrum, rotenone, derris, cube, DDT and the like. Such a combination is particularly effective where the paralytic and lethal action of the insecticide is slow.

Although this invention has been describe with reference to preferred illustrative embodiments thereof it will be apparent to those skilled in the art that the principles of this invention may be embodied in other forms but within the scope of the appended claims.

What we claim is:

1. The N-(a-etherified-acetyl) carbamic acid esters having the formula:

R- (O-A) n-O-CH2CONHCQOR' wherein R. is selected from the group consisting of halogenated aryl and hydrocarbon radicals selected from thegroup consisting of alkyl, aryl and aralkyl, A is divalent lower alkylene and n is a positive integer no higher than 2; and R' is selected from the group consistingof heterocyclic wherein the hetero atom is oxygen, hydrocarbon radicals selected from the group' consisting of alkyl, aralkyl and cycloalkyl, and radicals of the type R."-O-X- wherein X is divalent lower alkylene and R" is a hydrocarbon radical selected from the group consisting of alkyl, aralkyl and aryl.

2. The N-(a-etherified-acetyl) carbamic acid esters having the formula:

Alk- O-A) n-O-CHZCONHCOOR' wherein Alk is alkyl, A is divalent lower alkylene, n is a positive integer no higher than 2 and R is selected from the group consisting of heterocyclic wherein the hetero atom is oxygen,hydrocarbon radicals selected from the group consisting of alkyl, aralkyl and cycloalkyl, and radicals of the type R-O--X- wherein X is divalent lower alkylene and R is a hydrocarbon radical selected from the group consisting of alkyl, aralkyl and aryl.

3. Butyl N-p-butoxyethoxyacetyl carbamate. 4. Butyl N-p-ethoxyethoxyacetyl carbamate. 5. Isoamyl N-fi-butoxyethoxyacetyl carbamate. 6. The process of preparing N-(a-etherifiedacetyl) carbamic acid esters which comprises reacting an u-etherified acetyl halide having the following formula:

wherein R is selected from the group consisting of halogenated aryl and hydrocarbon radicals selected from the group consisting of alkyl, aryl 6 and aralkyl, A is divalent lower alkylene and n is a positive integer no higher than 2 and Y is halogen with a carbamic acid ester having the following formula:

NI-IzCOOR' wherein R is selected from the group consisting of heterocyclic, hydrocarbon radicals selected from the group consisting of alkyl, aralkyl and cycloalkyl, and radicals of the type R"-O-X- wherein X is divalent lower alkylene and R" is a hydrocarbon radical selected from the group consisting of alkyl, aralkyl and aryl.

'7. The N-(a-etherified-acetyl) carbamic acid esters having the formula:

wherein Alk and Alk' are alkyl.

KARL H. WEBER. LOWELL B. KILGOREL REFERENCES CITED The following references are of record in the file of this patent:

UNITED STATES PATENTS Number Name Date 1,237,413 Thorp Aug. 21, 1917 2,306,599 Engel et a1 Dec. 29, 1942 

1. THE N-(A-ETHERFIED-ACETYL) CARBAMIC ACID ESTERS HAVING THE FORMULA: 